Nanog induces hyperplasia without initiating tumors

作者：Fischedick Gerrit; Wu Guangming; Adachi Kenjiro; Arauzo Bravo Marcos J; Greber Boris; Radstaak Martina; Koehler Gabriele; Tapia Natalia; Iacone Roberto; Anastassiadis Konstantinos; Schoeler Hans R; Zaehres Holm

来源：Stem Cell Research, 2014, 13(2): 300-315.

DOI：10.1016/j.scr.2014.08.001

Though expression of the homeobox transcription factor Nanog is generally restricted to pluripotent cells and early germ cells, many contradictory reports about Nanog%26apos;s involvement in tumorigenesis exist. To address this, a modified Tet-On system was utilized to generate Nanog-inducible mice. Following prolonged Nanog expression, phenotypic alterations were found to be restricted to the intestinal tract, leaving other major organs unaffected. Intestinal and colonic epithelium hyperplasia was observed-intestinal villi had doubled in length and hyperplastic epithelium outgrowths were seen after 7 days. Increased proliferation of crypt cells and downregulation of the tumor suppressors Cdx2 and Klf4 was detected. ChIP analysis showed physical interaction of Nanog with the Cdx2 and Klf4 promoters, indicating a regulatory conservation from embryonic development. Despite downregulation of tumor suppressors and increased proliferation, ectopic Nanog expression did not lead to tumor formation. We conclude that unlike other pluripotency-related transcription factors, Nanog cannot be considered an oncogene.

• 出版日期2014-9